Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2022 May 11;13:2572. doi: 10.1038/s41467-022-30149-2

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

PMC Copyright notice

Fig. 5 — a Structure of BC-DXI-32982 (DXI hereafter). b Inhibitory effect of DXI on the binding of DX2 and KRAS4B. Binding pair of PRKACA and PRKAR2A was used for checking the binding specificity. N.D. denotes “not determined” in the tested range of dose. The experiment was independently repeated thrice and error bars denote S.D. Data are presented as mean values ± S.D. P value is from the two-sided t test. c Endogenous immunoprecipitation showing the interaction between DX2 and KRAS in H460 cells treated with DXI. Results are representative of at least three independent experiments. d In vitro pull-down assay showing direct inhibition of DXI on the binding of DX2 and KRAS4B. DXI was incubated with the mixture of cellular extracts expressing GFP-KRAS4B and the purified GST-DX2 proteins. Results are representative of at least three independent experiments. e Suppression of KRAS level via DXI. H460 cells treated with various concentration of DXI for 18 h were subjected to immunoblotting and RT-PCR. Results are representative of at least three independent experiments. f Ubiquitination assay analyzing DXI-mediated ubiquitination of KRAS. Results are representative of at least three independent experiments. g Heat map showing EC₅₀ of DXI on lung, colorectal, and pancreatic cancer cell lines expressing different levels of DX2 (Supplementary Fig. 12a). In each type of cancers, the maximum and minimum EC₅₀ values were represented as blue color with the highest and lowest intensity, respectively, and the rests were graded according to their relative values. h, i In vivo efficacy of DXI on tumor growth. Mice (n = 3) xenografted with H460 cells were intraperitoneally injected with DXI (1 or 5 mg/kg) five times in 12 d (h). Mice (n = 6) xenografted with HCC1588 or A549 cells were intravenously injected with DXI (5 mg/kg) five times during the experiment (i). All error bars represent the standard deviation (S.D.). P value is from the two-sided t test. Source data are provided as a Source data file.